Fungal infections

Trained immunity: Fungal infections

Research topic

Candida albicans (C. albicans) is a commensal fungus that colonizes the gastrointestinal (GI) tract of 40-60% of healthy adults. However, invasive candidiasis occurs all too frequently in hospitalized and immunocompromised patients, causing a severe disease associated with high mortality 1. With the increasing incidence of drug-resistant, multi-drug-resistant and also non-albicansCandida (NAC) species, it is imperative to develop alternative strategies to prevent and treat these life-threatening infections. Our working hypothesis is that understanding the ecology and evolution of Candida species in the mammalian gastrointestinal tract, and their complex and dynamic interactions with the host immune system and with other commensal microbes, will lead to the development of novel probiotic or vaccine strategies for the prevention of hospital-acquired fungal infections 2.

Using a combination of experimental and computational tools, our lab aims at understanding the evolution of host-pathogen interactions, the ecology of bacterial-fungal interactions, and the role played by the immune system and the gut microbiome in these processes. Studying bacterial-fungal interactions, we identified the transcription factor MIG1, expressed in C. albicans, to confer resistance against weak organic acids (WOAs) released by commensal bacteria to control yeast growth 3-5. In terms of host-fungal interactions, we reported the exposure of β-glucan on the surface of the Candida cell wall to highly correlate with competitive fitness of the fungi colonizing the mammalian GI tract 6, and that intraspecies diversity across different C. albicans clinical isolates is associated with large variation in immune responses along the commensalism-pathogenicity axis 7. Our group also recently developed a meta-total RNA sequencing (MeTRS) method based on shotgun sequencing of total RNA, which provides a valuable alternative platform for large-scale profiling of complex microbiomes, including bacteria and fungi, in human stool samples 8.

Beyond dissecting such complex and dynamic traits in the GI tract, we are actively collaborating with the group of Prof. Mihai Netea at Radboud University Medical Centre (Nijmegen, Netherlands) on the Human Functional Genomics Project (500FG cohort study) 9,10 and are currently exploring how the power of innate immune memory, a.k.a. ‘trained immunity’, can be harnessed to develop vaccines against candidiasis and other opportunistic infections.